PubMed Health⌕ Search

Biomedical subjects

J Niedermeyer

Publications and source records attributed to J Niedermeyer.

At least 37 records · Page 2Linked to original sources
PubMed2000

A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group.

OBJECTIVE: We sought to compare the acute hemodynamic effects of inhaled nitric oxide (NO) and aerosolized iloprost in primary pulmonary hypertension (PPH). BACKGROUND: Inhalation of the stable prostacyclin analogue iloprost has recently been described as a novel therapeutic strategy for PPH and may offer an alternative to continuous intravenous infusion of prostacyclin or inhalation of NO. METHODS: During right heart catheterization, 35 patients with PPH sequentially inhaled 40 ppm of NO and 14 to 17 microg of iloprost, and the effects on hemodynamics and blood gases were monitored. RESULTS: Both NO and iloprost caused significant increases in cardiac output, mixed-venous oxygen saturation and stroke volume as well as significant decreases in pulmonary artery pressure and pulmonary vascular resistance, whereas only inhaled iloprost significantly increased the arterial PO2 (p = 0.01). Compared with inhaled NO, aerosolized iloprost was more effective in reducing pulmonary artery pressure (-8.3 +/- 7.5 mm Hg vs. -4.3 +/- 8.8 mm Hg; p = 0.0001) and the pulmonary vascular resistance (-447 +/- 340 dynes x s x cm(-5) vs. -183 +/- 305 dyne x s x cm(-5); p < 0.0001). Furthermore, aerosolized iloprost caused a significantly greater increase of the cardiac output compared with NO (+0.7 +/- 0.6 liter/min vs. +0.3 +/- 0.4 liter/min; p = 0.0002) and had a more pronounced effect on the mixed-venous oxygen saturation (p = 0.003). CONCLUSIONS: During acute drug testing, aerosolized iloprost was more potent than inhaled NO as a pulmonary vasodilator in PPH at the doses used in this study.

Administration, Inhalation↗
PubMed2000

Targeted disruption of mouse fibroblast activation protein.

Human fibroblast activation protein (FAP), a member of the serine prolyl oligopeptidase family, is a type II cell surface glycoprotein selectively expressed by fibroblastic cells in areas of active tissue remodeling, such as the embryonic mesenchyme, areas of wound healing, the gravid uterus, and the reactive stroma of epithelial cancers. Homologues of FAP have been identified in the mouse and Xenopus laevis. FAP is a dual-specificity enzyme that acts as a dipeptidyl peptidase and collagenase in vitro. To explore the role of FAP in vivo, Fap(-/-) mice were generated by homologous recombination. RNase protection analysis and reverse transcription-PCR confirmed the absence of full-length Fap transcripts in mouse embryonic tissues. No FAP protein was detected in Fap(-/-) animals by immunohistochemistry, and no FAP-specific dipeptidyl peptidase activity was found. We report that Fap(-/-) mice are fertile, show no overt developmental defects, and have no general change in cancer susceptibility.

Aging↗
PubMed1999

Pulmonary hypertension after splenectomy?

BACKGROUND: A high prevalence of asplenia has been observed in patients with unexplained pulmonary hypertension. OBJECTIVE: To describe the clinical and histopathologic characteristics of patients with postsplenectomy pulmonary hypertension and to compare the prevalence of surgical asplenia in patients with idiopathic pulmonary hypertension and patients with other pulmonary diseases. DESIGN: Case series and case-control study. SETTING: University hospital in Hannover, Germany. PATIENTS: 61 patients with pulmonary hypertension and 151 lung transplant recipients. RESULTS: The prevalence of asplenia in patients with pulmonary hypertension was 11.5% (95% CI, 4.7% to 22.2%) compared with 0% (CI, 0% to 3.2%) in those without pulmonary hypertension (P < 0.001). Histopathologic examination of lung specimens from patients with postsplenectomy pulmonary hypertension showed intimal fibrosis, plexiform lesions, and abundant thrombotic lesions. CONCLUSION: Patients who have had splenectomy may be at increased risk for developing pulmonary hypertension.

Case-Control Studies↗
PubMed1999

Lung transplantation--10-year experience.

OBJECTIVE: The experience at our institution with various forms of lung transplantation (heart-lung, double lung and single lung) from December 1987 to September 1998 is reviewed and discussed. METHODS: During this decade, 282 procedures (46 heart-lungs (HLTx), 142 double lungs (DLTx) and 94 single lungs (SLTx)) have been performed in 258 patients (140 male, 118 female; age: 38 +/- 13 years). Major indications included pulmonary fibrosis (n = 73), obstructive lung disease (n = 55), cystic fibrosis (n = 48), primary pulmonary hypertension (n = 36), secondary pulmonary hypertension (majority Eisenmenger's syndrome) (n = 30), and retransplantation (n = 24). RESULTS: Early postoperative mortality (<90 days) was 13.9% (n = 36). The 1-, 3-, and 5-year survival rates in all recipients was 77, 70 and 63%, respectively. There was no significant difference in 1-year survival rates between the different procedures (HLTx: 78%, DLTx: 77%, SLTx: 77%). Significantly better 1-year survival was achieved in patients with cystic fibrosis (89%), pulmonary fibrosis (81%), obstructive lung disease (74%), and Eisenmenger's syndrome (83%) when compared to patients with primary pulmonary hypertension (55%). Survival rates remained unchanged during this period despite expanding indications during the last years. Causes of death in 90 recipients (HLTx: n = 19, DLTx: n = 37, SLTx: n = 34) included sepsis (n = 42), obliterative bronchiolitis (n = 28), cardiac failure (n = 5), and early allograft dysfunction (n = 2). Freedom from bronchiolitis obliterans syndrome (BOS) (>stage I ISHLT) was 80% at 1 year and 45% at 5 years. CONCLUSIONS: Lung transplantation offers a true therapeutic option with good early and midterm results. Yet, chronic graft dysfunction represents a major obstacle for long-term benefit of this procedure.

Adolescent↗
PubMed1999

Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension.

Assessment of cardiac output is an important part of the management of patients with pulmonary hypertension. The accuracy of the thermodilution technique in patients with low cardiac output or severe tricuspid regurgitation has been questioned. To address this issue, we simultaneously compared 105 cardiac output measurements by the Fick method and thermodilution in 35 patients with pulmonary hypertension. Moreover, we evaluated the acetylene rebreathing technique, a noninvasive method of determining cardiac output. The mean difference +/- 95% limit of agreement between thermodilution and the Fick method was +0.01 +/- 1.1 L/min. The mean difference +/- 95% limit of agreement between acetylene rebreathing and the Fick method was -0.23 +/- 1.14 L/min. Neither the mean agreement nor the 95% limits of agreement of both thermodilution and acetylene rebreathing with the Fick method were affected by the presence of low cardiac output or severe tricuspid regurgitation. We conclude that thermodilution and acetylene rebreathing are useful tools for assessing cardiac output in patients with pulmonary hypertension, even in the presence of low cardiac output or severe tricuspid regurgitation.

Acetylene↗
PubMed1999

[Lung transplantation in Hanover: an interim balance-sheet after ten years].

BACKGROUND: We reviewed our experience with various forms of lung transplantation (heart-lung [HLTx], bilateral lung [BLTx] and single lung [SLTx]) from December 1987 to September 1998 at Hannover University. PATIENTS: In 258 patients 282 procedures (46 HLTx, 142 BLTx and 94 SLTx) were performed. Major indications were pulmonary fibrosis (n = 73), obstructive lung disease (n = 55), cystic fibrosis (n = 48), primary pulmonary hypertension (PPHT, n = 36), secondary pulmonary hypertension (n = 30) and retransplantation (n = 24). RESULTS: The 1-, 3- and 5-year survival rates in all 258 recipients were 77%, 70% and 63% respectively. Significantly better 1-year survival was noted in patients with cystic fibrosis (90%), pulmonary fibrosis (81%), obstructive lung disease (71%) and secondary pulmonary hypertension (83%) when compared to patients with primary pulmonary hypertension (58%). There was no significant difference in actuarial 1-year survival rates between the different procedures (HLTx 78%, BLTx 77%, SLTx 77%). Bronchiolitis obliterans syndrome (BOS) proved to be the major obstacle for long term survival. Actuarial freedom from BOS was 80% at 1 year and only 45% at 5 years. Various treatment strategies including augmentation of immunosuppression could only temporarily halt the deterioration of lung function in the majority of patients with BOS. CONCLUSIONS: Lung transplantation provides a true therapeutic option for patients with endstage lung disease. However, improved long term outlook will depend on a better understanding and treatment of bronchiolitis obliterans.

Adolescent↗
PubMed1998

Mouse fibroblast-activation protein--conserved Fap gene organization and biochemical function as a serine protease.

The human fibroblast-activation protein (FAP), a member of the serine protease family, was discovered as an inducible type-II cell-surface glycoprotein selectively expressed by reactive stromal fibroblasts of epithelial cancers and healing wounds. Antibodies directed against human FAP have a clinical use for antibody-based tumor imaging. As part of an effort to generate animal models of FAP expression in epithelial tumorigenesis and wound healing, we previously cloned the cDNA encoding the mouse FAP homolog. In this study, we used PCR/restriction-fragment length polymorphism, identified in interspecific back-crosses between Mus musculus and Mus spretus, to map the Fap gene locus to a region of mouse chromosome 2, known to be syntenic to the previously identified FAP gene locus on human chromosome 2q23. The Fap gene spans approximately 60 kb and contains 26 exons ranging in size from 46 bp to 195 bp. This genomic organization is very similar to that of the human FAP locus. Similar to the gene encoding dipeptidyl peptidase IV (DPP IV), the nucleotides encoding the serine protease consensus motif, WGWSYGG, are split between two exons, a feature distinct from classical serine proteases. Consistent with the similarity to DPP IV, a chimeric FAP fusion protein expressed in a baculovirus system has dipeptidyl peptidase activity.

Animals↗
PubMed1997

Mouse fibroblast activation protein: molecular cloning, alternative splicing and expression in the reactive stroma of epithelial cancers.

The growth of solid neoplasms requires the recruitment of a supporting stroma. In most epithelial cancers, this stromal compartment comprises newly formed blood vessels and abundant, reactive stromal fibroblasts. Tumor stromal fibroblasts are not transformed but differ from resting fibrocytes in normal adult tissues by an altered pattern of gene expression. In human cancers, this includes induction of the cell-surface-bound fibroblast-activation protein (FAP), a member of the serine protease family encoded by the FAP gene on chromosome 2. In this study, we have cloned a complementary DNA for Fap, the murine homologue of FAP. The predicted murine FAP protein, mFAP, shares 89% amino-acid-sequence identity with human FAP, including a perfectly conserved catalytic triad. Cultured mouse embryo fibroblasts and mouse embryonic tissues were found to express Fap transcripts. In addition, the host-derived, fibroblast-rich stroma of human epithelial-cancer xenografts grown in immunodeficient mice also expresses Fap. Sequencing of reverse-transcription-PCR products indicates that 3 distinct Fap splice variants can be detected in tissues. Our findings suggest a close similarity in structure and tissue expression of FAP in different species. By extending the analysis of FAP to the mouse, new in vivo test systems become available for genetic and therapeutic manipulations and for the study of FAP regulation and function in embryonic development and in epithelial cancers.

Adenocarcinoma↗
PubMed1997

Classification of Sneddon's syndrome.

BACKGROUND: The combination of generalized broken ("racemose") livedo and cerebrovascular accidents is referred to as "Sneddon's syndrome". Although several pathogenetic factors have been suggested the aetiology of Sneddon's syndrome is unknown. Furthermore, considerable variability of patient characteristics gives rise to the question whether "Sneddon's syndrome" denotes a homogeneous disease entity at all. We hypothesized that the diagnosis "Sneddon's syndrome" can be broken down into different subgroups according to possible aetiologic factors. PATIENTS AND METHODS: Thirty-two patients with the combination of generalized broken livedo and cerebrovascular accidents were evaluated by clinical examination, routine diagnostic procedures, MRI of the brain, echocardiography, vascular ultrasound, immunologic and haemostaseologic testing. Patient groups were formed, depending on (1) whether or not an additional feature with a possibly aetiologic role for Sneddon's syndrome was present, and (2) which kind of feature it was. RESULTS: In 16 out of 32 patients, diagnostic features with an implication for the pathogenesis of Sneddon's syndrome could be identified. An autoimmune disorder was diagnosed in six patients. A thrombophilic state was detected in six patients. Three patients had preexisting atherosclerosis. One patient suffered from an embolizing atrial myxoma. Extent and kind of cerebral pathology differed between patient groups as did the kind of cardiac involvement. CONCLUSION: Sneddon's syndrome is not a homogeneous disease entity. Patients should be classified as "primary Sneddon's syndrome" if no aetiologic factor can be detected. On clinical grounds, this from differs from several varieties of "secondary Sneddon's syndrome" which occurs mainly as part of an autoimmune disorder or in a thrombophilic state.

Adult↗
PubMed1996

Seasonal onset of bronchiolitis obliterans syndrome in lung transplant recipients.

BACKGROUND: Bronchiolitis obliterans syndrome is the major complication in long-term survival of patients with lung transplants. Bronchiolitis obliterans syndrome is thought to represent a form of chronic allograft rejection and is associated with obstructive airways disease. Viral infections or other exogenous factors may trigger this condition. METHODS: Because respiratory viral infections show seasonal clustering we studied seasonal onset of bronchiolitis obliterans syndrome in 157 lung and heart-lung transplant recipients. Individual baseline values of forced expiratory volume in 1 second were evaluated according to the International Society for Heart and Lung Transplantation criteria. For bronchiolitis obliterans syndrome classification, values of forced expiratory volume in 1 second were determined by the average of two measurements made at least 1 month apart. Onset of bronchiolitis obliterans syndrome was defined as the date of the initial pulmonary function test showing a persistent decline of forced expiratory volume in 1 second. Other factors causing obstructive airways disease were excluded. RESULTS: Forty-nine patients (31%) showed development of bronchiolitis obliterans syndrome (n = 10 stage I, n = 13 stage II, n = 26 stage III) with onset of bronchiolitis obliterans syndrome 507 +/- 372 days (mean +/- standard deviation) after transplantation. Baseline value of forced expiratory volume in 1 second was reached at 270 +/- 231 days. Between January and March of each year onset of bronchiolitis obliterans syndrome developed in 23 patients (47%). In the second (April to June) and third (July to September) quarters a persistent decline of pulmonary function test results developed in 13 (27%) and 12 (24%) patients, respectively, whereas only 1 patient (2%) showed deterioration between October and December (p < 0.001). CONCLUSIONS: Seasonal clustering of onset of bronchiolitis obliterans syndrome might thus indicate underlying unknown infectious triggers.

Adult↗
PubMed1993

[Value of transesophageal echocardiography in diagnosis of diseases of native heart valves].

In the clinical management of patients with valvular heart disease, transthoracic echocardiography (TTE) combined with Doppler has become the central diagnostic tool during the past decades. The development of transesophageal echocardiography (TEE) has led to an improved image quality especially of structures distant to the chest wall. However, since TEE is a semi-invasive technique, its use has to be considered carefully. In aortic valve disease, TEE facilitates a detailed study of valve morphology and allows sufficiently reliable planimetry of aortic valve area, at least when the multiplane approach is used. This is particularly helpful in those patients where Doppler interrogation from precordial windows fails. Aortic regurgitation is diagnosed more frequently by TEE color-flow imaging than by TTE; however, both techniques allow only semiquantitative assessment of the severity of regurgitation. TEE is also superior to TTE in defining the exact origin site, number and configuration of regurgitant jets in patients with mitral insufficiency. In particular minimal and mild mitral regurgitation is more easily detected by TEE than by TTE. The same is true for flail mitral leaflets, chordal and papillary muscle rupture, and potentially also for discrete forms of mitral valve prolapse. During surgery, TEE can be considered as an ideal tool for immediate assessment of the results of mitral valve reconstruction. Calculation of pressure gradients and valve area by TEE Doppler analysis shows comparable results to precordial studies. When multiplane TEE is available, Doppler beam alignment may become even improved in selected cases with severely excentric flow jet orientation. In addition, TEE provides of course clinically important information concerning presence or absence of atrial and particularly atrial appendage thrombi as well as of spontaneous echo contrast in patients with stenotic mitral valve. This is not only helpful regarding the decision for anticoagulation but it may also be critical in the selection of candidates for percutaneous mitral balloon valvuloplasty. TEE does also allow the morphological and functional evaluation of tricuspid and pulmonic valves. In this context, the use of biplane or multiplane TEE probes is superior to that of monoplane devices. However, currently available data does not provide unequivocal evidence that the analysis of tricuspid and pulmonic valve disease by TEE is superior to the conventional transthoracic approach.

Blood Flow Velocity↗
PubMed1993

[The value of echocardiography in diagnosis of acute pulmonary embolism].

The technology of echocardiographic imaging is now widely available and has become increasingly important in the diagnosis of severe pulmonary embolism. In this setting transthoracic two-dimensional echocardiography (TTE) permits a rapid and non-invasive bed-side assessment of right ventricular size and systolic function. Doppler techniques facilitate precise measurements of pulmonary arterial pressures. These parameters can be easily followed after initiating therapy and allow to recognize patients refractory to the chosen therapeutic regimen. With transesophageal echocardiography (TEE), as well as with TTE, direct visualization of thromboembolic material within the central pulmonary arteries or the right heart chambers is possible. TEE, however, is more sensitive than TTE in detecting thrombotic or embolic material. It is also superior in the diagnosis of a patent foramen ovale which may indicate impending paradoxical embolism. The role of intravascular ultrasound imaging in clinical practice is not clear yet. It may be helpful in the localization and differential diagnosis of thromboembolic material in the pulmonary vascular bed.

Acute Disease↗
PubMed1993

[Acute pulmonary embolism].

In the absence of significant symptoms and signs the diagnosis of pulmonary embolism remains difficult. Sensitivity and specificity of laboratory tests, chest x-ray, ECG, echocardiography and venous studies on their own is low. Ventilation-perfusion scanning establishes or excludes the diagnosis only in those patients with "high-probability" or "normal" scanning results. The diagnosis of pulmonary embolism should be made by combining clinical assessment, several diagnostic techniques, and, finally, pulmonary angiography in doubtful cases. Heparin remains the standard therapy for patients with stable hemodynamics. Thrombolytic therapy is recommended in hemodynamically compromised patients. In short-term dose regimens the thrombolytic agents urokinase and rt-PA seem to be equally effective. So far, however, no study has proven that thrombolytic therapy significantly reduces mortality in pulmonary embolism.

Acute Disease↗